Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway

Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.

Comparative proteomes change and possible role in different pathways of micro RNA-21a-5p in a mouse model of spinal cord injury

Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly understood.In this study,a modified Allen's weight drop was used to establish a mouse model of spinal cord injury.A proteomics approach was used to understand the role of differential protein expression with miR-21 a-5 p knockdown,using a mouse model of spinal cord injury without gene knockout as a negative control group.We found that after introducing miR-21 a-5 p knockdown,proteins that played an essential role in the regulation of inflammatory processes,cell protection against oxidative stress,cell redox homeostasis,and cell maintenance were upregulated compared with the negative control group.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified enriched pathways in both groups,such as the oxidative phosphorylation pathway,which is relevant to Parkinson's disease,Huntington's disease,Alzheimer's disease,and cardiac muscle contraction.We also found that miR-21 a-5 p could be a potential biomarker for amyotrophic lateral sclerosis,as miR-21 a-5 p becomes deregulated in this pathway.These results indicate successful detection of some important proteins that play potential roles in spinal cord injury.Elucidating the relationship between these proteins and the recovery of spinal cord injury will provide a reference for future research of spinal cord injury biomarkers.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Shandong University of China on March 5,2014.

Circulating MicroRNAs as Potential Biomarkers in the Diagnosis of Neurosyphilis: A Case Control Study

Objective:Laboratory diagnosis of neurosyphilis(NS)remains a great challenge.This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS,non-neurosyphilis,and healthy controls(HCs).Methods:We analyzed miRNA expression profiles in peripheral blood mononuclear cells(PBMCs)from six patients with NS,eight patients with secondary syphilis(SS),and five HCs using microarray technology.The differentially expressed miRNAs were validated in 33 NS samples,31 SS samples,and 30 HC samples using TaqMan miRNA real-time qPCR(qRT-PCR).Results:Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs.Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR.All miRNAs were upregulated in SS and NS samples compared with HC.qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort(76 samples)showed that the average expression levels of nine miRNAs were higher in SS than in NS(SS:0.185,NS:0.136,P=3.8E-10),while the expressions of the other four miRNAs were lower in SS than in NS(SS:0.000757,NS:0.000873,P=0.022).ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs,1.00 for distinguishing NS patients from HCs,1.00 for distinguishing SS and NS patients from HCs,and 0.968 for distinguishing NS from SS patients.Conclusion:The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS.Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.